As many as 40% of general medical hospital admissions are linked to alcohol, and alcohol dependence (AD) is a risk factor for readmission (a marker of poor quality of care for which hospitals are financially penalized). Yet most inpatients with AD receive no effective treatment, leaving them vulnerable to both alcohol-specific consequences, and the deleterious effects of untreated AD on medical conditions and related healthcare utilization. Pharmacotherapy for AD (oral tablet naltrexone, PO-NTX; extended-release injectable naltrexone, XR-NTX) has efficacy but unlike treatments for other medical conditions routinely started at hospital discharge it is rarely prescribed. In addition, litle is known about the effectiveness of pharmacotherapy under real-world conditions compared to other clinically available options, and clinicians have little evidence upon which to base decisions to prescribe a costly (per dose) monthly injection or a daily tablet (that may be less adhered to). Therefore, this proposal (in response to PAS-10-273 Clinically Relevant Comparative Effectiveness of Alcoholism Treatments) aims to test the effectiveness of beginning XR-NTX and PO-NTX for AD in medical inpatients at the time of hospital discharge in a pragmatic comparative effectiveness randomized trial. In the Alcohol Dependence hospital Treatment (ADOPT) study, inpatients will receive counseling in the hospital and at follow-up that is feasible in medical settings, and be randomly assigned to monthly XR-NTX, daily PO- NTX or no medication. The primary outcome is percent heavy drinking days; additional outcomes of interest include alcohol consequences, medical healthcare utilization (hospital and emergency department), AD treatment utilization, and costs. The main hypotheses are that 1) XR-NTX will have greater effectiveness than PO-NTX and 2) than no medication, and that 3) PO-NTX will have greater effectiveness than no medication on drinking, consequences and utilization. Cost-effectiveness analysis will compare the costs and outcomes of the three alternatives. Patient factors that moderate effectiveness will be explored. The study is innovative in its design as a pragmatic comparative effectiveness trial, and because it addresses a question that is unanswered but highly relevant. It is timely in that a national accreditation body recently implemented quality performance measures of AD treatment at hospital discharge despite the absence of evidence for effectiveness in that circumstance. The significance of the study is that results will provide guidance for clinicians and policymakers regarding initiation of pharmacotherapy for alcohol dependence for patients at high risk for costly health consequences who largely receive no effective care at the time of hospital discharge.